胃癌化疗现状与进展12009-10.pptVIP

可切除胃癌的术前化疗 (新辅助化疗) 新辅助化疗的适应征 新辅助化疗的目标： 实现肿瘤降期；提高手术切除率 减少术后复发转移 延长患者生存期 新辅助化疗适用于： 无远处转移的局部进展期胃癌T3-T4或N+（2A） INT-0116 trial  INT0116研究 确立了具有复发高危的局部晚期胃癌和与食管接合部 的胃癌术后化放疗的标准治疗方案地位。正是基于该研究 的良好结果，胃癌术后的辅助放化疗被收入了NCCN。 FLAGS临床失败原因解析 S1作用机制: 1. S1的活化依赖于肝药酶,其疗效与细胞色素酶P450(CYP) 2A6 的基因多态性密切相关,该基因在不同人种和不同个体间存在较大差异,故该药物有效浓度和毒性反应的种族个体差异较大 2. 吉美嘧啶为DPD酶抑制剂,人群中呈DPD酶缺乏,加用DPD酶抑制剂可导致较严重的5Fu蓄积,并不可避免的限制了S1的治疗窗. 用药剂量: 鉴于作用机制的限制,S1在多项临床中剂量各不相同,本研究采用4周用法,连用3周停1周,也可能是导致失败的原因. 胃癌分子靶向治疗 国际多中心III期临床试验 观察两组患者的无进展生存期、总生存期和近期疗效 FLAGS phase III study design. Primary endpoint: overall survival. Secondary endpoints: PFS, safety, time to treatment failure, overall response rate. Ajani et al. ASCO GI 2009 Median overall survival was 8.6 months in patients receiving CS compared with 7.9 months for those receiving CF. Ajani et al. ASCO GI 2009 Median progression-free survival was 4.8 months in patients receiving CS compared with 5.5 months for those receiving CF. Ajani et al. ASCO GI 2009 Incidence of Grade 3/4 hematological adverse events in the 2 treatment arms. Ajani et al. ASCO GI 2009 Incidence of Grade 3/4 non-hematological adverse events in the 2 treatment arms. Ajani et al. ASCO GI 2009 Renal- and liver-related toxicities. It is worth noting that liver-related toxicities are higher for CS. Ajani et al. ASCO GI 2009 CS did not improve overall survival compared with CF. There was no difference between CS and CF in secondary endpoint efficacy markers. CS had an improved safety profile compared with CF. However, the dose of cisplatin used in CS was 75% of that used in CF and the dose of S-1 was reduced by 34% from that used in an earlier Japanese study. Ajani et al. ASCO GI 2009 关于欧美与亚洲结果差异的解释： 诸多学者对FLAGS研究结果心存疑虑，因为该研究中S-1剂量为25 mg/m2 bid，其强度仅为亚洲国家的常用剂量（40 mg/m2 bid）的70%。另外CS组顺铂的剂量（75 mg/m2 ）也小于CF组（100 mg/m2）。S-1的剂量强度不足可能影响了CS的疗效，而其安全性提高的部分原因可能正是顺铂剂量的减小。 S-1的活化依赖于肝药酶，其疗效与细胞色素P450 2A6（CYP2A6）基因多态性密